This was designed to prove that Oxford was older than Cambridge University, and has been described by a modern writer as a "remarkable achievement for a young scholar of twenty-eight.
He was rewarded by appointment in 1634 to the new position of Keeper of the Archives, in which role he obtained a new royal charter for Oxford to confirm its rights and privileges, and helped the university in its disputes with the city authorities.
Despite the assistance of his father's patron Thomas Sackville, 1st Earl of Dorset (Lord High Treasurer and Chancellor of the University), he failed to be elected to a fellowship at Merton College, Oxford.
He studied with the mathematician Thomas Allen, encountering modern developments in astronomy and navigation, and also learned French, Italian and Hebrew.
He became a Fellow of Corpus Christi in 1606, and was ordained in the following year; although he later became vicar of Rye, Sussex, he stayed in Oxford and the parish duties were undertaken by curates.
This has been described by Strickland Gibson (Keeper of the Archives at Oxford 1927–1945) as being "of a controversial character, and not of a kind to establish his reputation as a sound historian.
Twyne had been unable to find the reference to Alfred's visit to Oxford in any known manuscript of Asser's work, and challenged Camden about it.
[4] One more recent history of the university says that "even in his own time Twyne's opinions on this subject [i.e. when Oxford was founded] were received with amused tolerance by the better informed of English antiquaries.
It was published by the university printer, Joseph Barnes, who would have required guarantees for the costs: Gibson's view was that these were probably provided by Thomas Allen, with the Earl paying "the customary honorarium" as dedicatee.
[2] By 1623, Twyne had resigned his fellowship, apparently (according to the 17th-century Oxford historian Anthony Wood) to avoid having to choose which side to support in a dispute between the college president and the fellows.
[2] In 1630, Twyne was part of a new delegacy appointed by the new Chancellor of the University William Laud (who was also Archbishop of Canterbury) to revise the statutes.
The other members were Robert Pink (Warden of New College), Thomas James (Bodley's Librarian, later replaced on the committee by Peter Turner), and Richard Zouch (Regius Professor of Civil Law).
The vice-chancellor asked Turner to make a final revision, and requested that Twyne write a historical account of the previous attempts to reform the statutes as a preface.
The new statute governing the position noted the losses that Oxford had suffered because of the careless keeping of its archives, and the need for an experienced person to take charge of them and to advise the university's officers in defending its interests.
[13] Under Twyne and his successor as Keeper (Gerard Langbaine), the archives were moved into one of the rooms in the Tower of the Five Orders in the Bodleian Library; three of the wooden presses that were built at that time to store them are still in use.
[14] Twyne advised the university authorities in their disputes with the city fathers in relation to courts, licensing, markets and other matters.
A hard-working researcher and collector of manuscripts, he was highly regarded and consulted by the legal scholar John Selden, the historian William Camden and Archbishop James Ussher.