According to Anthony Wood, Jeffreys was descended from Matthew Jeffries of Wells and was a member of the Chapel Royal before 1643. His name does not, however, appear in the surviving court records, except as the composer of an anthem transcribed into the books of the Chapel Royal during the 1670s; nor can any evidence be found to link him with the Wells Cathedral musician. It seems more likely that Jeffreys came from Worcestershire. By his marriage he was related to the Salwey family of Stanford, and a pedigree of the Salweys, published in 1781, shows connections with the ‘Jefferies’ family of Holme Castle going back to the mid-16th century.
He was in the service of the Hatton family from at least 1631, when he set some verses by Sir Richard Hatton; the following year he collaborated with Peter Hausted, a Hatton protégé, in the stage work The Rivall Friends. Another poet in the Hatton circle, Thomas Randolph, provided the texts for three masque-songs and for the pastoral dialogue Why sigh you, swaine? Jeffreys was certainly in the employment of Sir Christopher Hatton (later 1st Baron Hatton) by 1633; in April of that year he made a ‘Cattalogue of Manuscripts of my Masters … at Moulton Park’. All this must cast further doubt on Wood's assertion that he had served at the Chapel Royal before 1643. By 1638 Jeffreys had moved to the village of Weldon, a few miles from Hatton's principal residence, Kirby Hall. In December 1637 he married Mary Peirs, the widowed daughter of Thomas Mainwaring, rector of Weldon and Dene. In his will, Mainwaring left £120 to his ‘affectionate son, George Jeffreys’; there were also bequests to Jeffreys's two children, Christopher, who in 1659 was a junior student at Christ Church, Oxford, and was said by Wood to be ‘excellent at the organ’, and Mary. Another son, Thomas, died in infancy.
In 1643 Jeffreys was summoned to Oxford to assist Hatton, now the king's Comptroller of Household, in what seems to have been a purely administrative capacity; however, his musical talents were soon put to use. Wood, Henry Aldrich (GB-Och 879, facing f.1) and, in the following century, Sir John Hawkins refer to his activities as organist at Christ Church, Hawkins adding the information that ‘choral service was performed there after a very homely fashion’. This comment implies that chapel services during the king's residence at Christ Church were performed in the manner of chamber music, a description which certainly applies to the few-voiced concertato motets by Italian composers of which Jeffreys made copies for performance, and also to many of the devotional songs he himself composed before 1646.
After the surrender of Oxford to the parliamentarian forces, Hatton fled to Paris, where he remained until 1656. Jeffreys returned to Weldon to resume his duties for the Hatton family; by 1649 he had become a senior Hatton servant, attending to their affairs in Northamptonshire as well as representing them in London. From this point onwards it is possible to follow his activities quite closely. About 250 letters he wrote to Hatton's son, Sir Christopher (later 1st Viscount Hatton), Lady Hatton and others (Hatton-Finch correspondence, GB-Lbl) are almost wholly concerned with administration of the Hatton estate, but, together with Jeffreys's will and the many comments he wrote into his autograph score book (Lbl Add.10338), they reveal a great deal about his character and personal circumstances. It is clear that, as a royalist and high churchman, it would have been difficult for him to find congenial employment as a musician under the Commonwealth. By the time of the Restoration he had acquired further property in Northamptonshire, including a manor house in Isham and several smaller dwellings that provided him with an income from rents. It is therefore not surprising that Jeffreys, no longer a young man in 1660, did not seek a post that would have given him recognition as a composer. The only work to be published in his lifetime was the two-part sacred song Erit gloria Domini. Nevertheless, to judge from the quantity of his music appearing in contemporary manuscripts other than the autographs, he seems to have been highly regarded by those who knew his work.