The available source materials on Cristofori's life include his birth and death records, two wills, the bills he submitted to his employers, and a single interview done by Scipione Maffei. From the latter, we have both Maffei's notes and the published journal article. Cristofori was born in Padua in the Republic of Venice. Nothing is known of his early life. A tale is told that he served as an apprentice to the great violin maker Nicolò Amati, based on the appearance in a 1680 census record of a "Christofaro Bartolomei" living in Amati's house in Cremona. However, as Stewart Pollens points out, this person cannot be Bartolomeo Cristofori, since the census records an age of 13, whereas Cristofori according to his baptismal record would have been 25 at the time. Pollens also doubts the authenticity of the cello and double bass instruments sometimes attributed to Cristofori.

Probably the most important event in Cristofori's life is the first one of which we have any record: in 1688, at age 33, he was recruited to work for Prince Ferdinando de Medici. Ferdinando, a lover and patron of music, was the son and heir of Cosimo III, who was one of the last of the Grand Dukes of Tuscany. Tuscany was at a time still a small independent state. It is not known what led Ferdinando to recruit Cristofori. The Prince traveled to Venice in 1688 to attend the Carnival, so he may have met Cristofori passing through Padua on his way home. Ferdinando was looking for a new technician to take care of his many musical instruments, the previous incumbent having just died. However, it seems possible that the Prince wanted to hire Cristofori not just as his technician, but specifically as an innovator in musical instruments. It would be surprising if Cristofori at age 33 had not already shown the inventiveness for which he later became famous.

The evidence — all circumstantial — that Cristofori may have been hired as an inventor is as follows. According to Stewart Pollens, there were already a number of qualified individuals in Florence who could have filled the position; however, the Prince passed them over, and paid Cristofori a higher salary than his predecessor. Moreover, Pollens notes, "curiously, [among the many bills Cristofori submitted to his employer] there are no records of bills submitted for Cristofori's pianofortes ... This could mean that Cristofori was expected to turn over the fruits of his experimentation to the court." Lastly, the Prince was evidently fascinated with machines (he collected over forty clocks, in addition to a great variety of elaborate musical instruments), and would thus be naturally interested in the elaborate mechanical action that was at the core of Cristofori's work on the piano.

Maffei's interview reports Cristofori's memory of his conversation with the Prince at this time:

che fu detto al Principe, che non volevo; rispos' egli il farò volere io.

which Giuliana Montanari translates as:

The prince was told that I did not wish to go; he replied that he would make me want to.

This suggests that the Prince may have felt that Cristofori would be a prize recruit and was trying to charm him into accepting his offer; consistent again with the view that the Prince was attempting to recruit him as an inventor.

In any event, Cristofori agreed to the appointment, at a salary of 12 scudi per month. He moved rather quickly to Florence (May 1688; his job interview having taken place in March or April), was issued a house, complete with utensils and equipment, by the Grand Duke's administration, and set to work. For the Prince, he tuned, maintained, and transported instruments; worked on his various inventions, and also did restoration work on valuable older harpsichords.

At this time, the Grand Dukes of Tuscany employed a large staff of about 100 artisans, who worked in the Galleria dei Lavori of the Uffizi. Cristofori's initial work space was probably in this area, which did not please him. He later told Maffei:

che da principio durava fatica ad andare nello stanzone in questo strepito

It was hard for me to have to go into the big room with all that noise (tr. Montanari)

Concerning how the Prince reacted to Cristofori's unhappy feelings, there is scholarly disagreement. According to Stewart Pollens, the interaction went as follows:

che da principio durava fatica ad andare nello stanzone in questo strepito; che fu detto al Principe, che non volevo; rispos' egli il farò volere io.

At the beginning it was very tiring of him to be in the large room with this deafening noise ... he told the prince that he did not want it so; the latter responded, he will do it, I wish it.

It can be seen that the very same words from the Maffei interview ("rispos' egli il farò volere io") have been interpreted by Montanari and Pollens in radically different ways, one portraying the Prince as charming if imperious, the other as harsh. In any event, Cristofori did eventually obtain his own workshop, usually keeping one or two assistants working for him.

During the remaining years of the 17th century, Cristofori invented two keyboard instruments before he began his work on the piano. These instruments are documented in an inventory, dated 1700, of the many instruments kept by Prince Ferdinando. Stewart Pollens conjectures that this inventory was prepared by a court musician named Giovanni Fuga, who may have referred to it as his own in a 1716 letter.

The spinettone, Italian for "big spinet", was a large, multi-choired spinet (a harpsichord in which the strings are slanted to save space), with disposition 1 x 8', 1 x 4'; most spinets have the simple disposition 1 x 8'. This invention may have been meant to fit into a crowded orchestra pit for theatrical performances, while having the louder sound of a multi-choired instrument. The other invention (1690) was the highly original oval spinet, a kind of virginals with the longest strings in the middle of the case.

Cristofori also built instruments of existing types, documented in the same 1700 inventory: a clavicytherium (upright harpsichord), and two harpsichords of the standard Italian 2 x 8' disposition; one of them has an unusual case made of ebony.

It was thought for some time that the earlier mention of the piano is from a diary of Francesco Mannucci, a Medici court musician, indicating that Cristofori was already working on the piano by 1698. However, the authenticity of this document is now doubted. The first unambiguous evidence for the piano comes from the 1700 inventory of the Medici mentioned in the preceding section. The entry in this inventory for Cristofori's piano begins as follows:

Un Arpicembalo di Bartolomeo Cristofori di nuova inventione, ch fa' il piano, e il forte, a' due registri principali unisoni, con fond di cipresso senza rosa..." (boldface added)

A large "Arpicembalo" by Bartolomeo Cristofori, of new invention that produces soft and loud, with two sets of strings at unison pitch, with soundboard of cypress without rose...

The term "Arpicembalo", literally "harp-harpsichord", was not generally familiar in Cristofori's day. Edward Good infers that this is what Cristofori himself wanted his instrument to be called. Our own word for the piano, however, is the result of a gradual truncation over time of the words shown in boldface above. The Medici inventory goes on to describe the instrument in considerable detail. The range of this (now lost) instrument was a mere four octaves, C - C'''. Another document referring to the earliest piano is a marginal note made by one of the Medici court musicians, Federigo Meccoli, in a copy of the book Le Istitutioni harmoniche by Gioseffo Zarlino. Meccoli wrote:

These are the ways in which it is possible to play the Arpicimbalo del piano e forte, invented by Master Bartolomeo Christofani [sic] of Padua in the year 1700, harpsichord maker to the Most Serene Grand Prince Ferdinand of Tuscany. (transl. Stewart Pollens)

According to Scipione Maffei's journal article, by 1711 Cristofori had built three pianos. One had been given by the Medici to Cardinal Ottoboni in Rome, and two had been sold in Florence.

Cristofori's patron, Prince Ferdinando, died at the age of 50 in 1713. There is evidence that he continued to work for the Medici court, still headed by the Prince's father Cosimo III. Specifically, a 1716 inventory of the musical instrument collection is signed "Bartolommeo Cristofori Custode", indicating that Cristofori had been given the title of custodian of the collection.

During the early 18th century, the prosperity of the Medici princes declined, and like many of the other Medici-employed craftsmen, Cristofori took to selling his work to others. The king of Portugal bought one of his instruments.

In 1726, the only known portrait of Cristofori was painted. It portrays the inventor standing proudly next to what is almost certainly a piano. In his left hand is a piece of paper, believed to contain a diagram of a Cristofori's piano action. Unfortunately, the portrait was destroyed in the Second World War, and only photographs of it remain.

Cristofori continued to make pianos until near the end of his life, continually making improvements in his invention. In his senior years, he was assisted by Giovanni Ferrini, who went on to have his own distinguished career, continuing his master's tradition. There is tentative evidence that there was another assistant, P. Domenico Dal Mela, who went on in 1739 to build the first upright piano.

In his declining years Cristofori prepared two wills. The first, dated January 24, 1729, bequeathed all his tools to Giovanni Ferrini. The second will, dated March 23 of the same year, changes the provisions substantially, bequeathing almost all his possessions to the "Dal Mela sisters ... in repayment for their continued assistance lent to him during his illnesses and indispositions, and also in the name of charity." This will left the small sum of five scudi to Ferrini. Pollens notes further evidence from the will that this reflected no falling out between Cristofori and Ferrini, but only Cristofori's moral obligation to his caretakers. The inventor died on January 27, 1731.