His first two publications were an edition of Richard Allestree's The Whole Duty of Man and Miscellaneous Works Serious and Humerous [sic] In Verse and Prose.

In 1743, Newbery left Reading, putting his stepson John Carnan in charge of his business there, and established a shop in London, first at the sign of the Bible and Crown near Devereux Court.

[7]: xiv In 1745 Newbery moved his firm to a more upmarket address at 65 St. Paul's Churchyard and named it the Bible and Sun, continuing to publish a mix of adult and children's titles.

Scholars have speculated that Goldsmith[11]: 36  or Giles and Griffith Jones[12] wrote The History of Little Goody Two-Shoes, Newbery's most popular book.

[12] Some sources credit Newbery with publishing the first edition of Mother Goose in England,[13] but others now say the book may have been planned, but was never actually produced.

[16] Some of his fortunes came from the patent and sales of Dr Robert James's Fever Powder, a medicine which claimed to cure gout, rheumatism, scrofula, scurvy, leprosy, and distemper in cattle.

Those he is known to have assisted include Johnson, who called him "Jack Whirler" for his constant activity and inability to sit still; and Goldsmith, who portrayed Newbery in The Vicar of Wakefield as Dr Primrose, "the friend of all mankind".

A Pretty Little Pocket-Book was a hodge-podge of information and games, including riddles and advice on a proper diet, but its primary message was "learn your lessons ... and one day you will ride in a coach and six.

"[12] "In Newbery's universe work is always rewarded and altruism pays dividends as reliably as Isaac Newton's laws of motion.

Francis (nephew) struck out on his own without legally inheriting any of John Newbery's publications, only a share of his newspaper interests.

Elizabeth carried on a successful, independent twenty-two year career, retiring in 1802 by selling the business to her successor, John Harris.

[18] According to the New Cambridge Bibliography of English Literature (NCBEL 2.120), Newbery "wrote, wholly or partly" and "edited or materially influenced" the following works: