He then joined a small Cambridge firm, Freeman & Bolles, that typeset and printed books for Little, Brown and Company.

After Bolles left in 1851, Houghton briefly entered a partnership with his cousin, Rufus Haywood, then with Edmund Hatch Bennett, before taking on full responsibility in 1855.

He became the main printer for publishers Ticknor and Fields, and, in 1863, was engaged by G. & C. Merriam Company to print and bind their new dictionary.

Hurd & Houghton struggled initially as a publisher, contending especially with lackluster periodical sales, and would not turn a profit until 1870.

In his 1891 will, he appointed daughter Elizabeth Harris Houghton "representative to nominate a patient for the free bed the testator established in the Cambridge hospital".