He was offered financial support by a wealthy relative for study at Oxford or Cambridge as an entry into a Church of England benefice, but he was attracted to the freedom of thought permitted Congregational ministers, and in 1852 entered New College, a Congregational institution at St. John's Wood, where he earned his BA with honours in the Greek Testament, botany, and animal physiology in 1855, and the Law subjects the following year, though in England he could not be awarded the LLB.

Family circumstances made this impractical, and he opted instead the pastorate of Saltaire, in Yorkshire, where a beautiful new Congregational church had just been completed, with funds provided by Sir Titus Salt.

The work was most congenial to him, but his lungs were badly affected by the inclement weather and his doctors, diagnosing tuberculosis, recommended he move to a milder climate.

The congregation moved into the new building in February 1861, and was soon swelled by Christians of other denominations, attracted by his "eloquence and manly and liberal approach to religion".

[3] He founded the North Adelaide Young Men's Society, which proved popular, and was credited with having a powerful influence for good.

[2] He several times refused calls to take over Sydney's Pitt Street Congregational Church, but in 1877 acquiesced, and preached his first sermon there on Easter Sunday.

He served there for 13 years, with a stipend of £1,000[2] (perhaps $200,000 in today's money), but Mrs. Jefferis was in poor health, and desired to return to her family in England, so in December 1889 he resigned and they travelled back to the "old country".

But London's weather affected the health of both Mr and Mrs Jefferis, and they removed to the milder climate of Torquay in Devonshire, where he served the Belgrave Congregational Church, which was suffering from a prevailing atmosphere of "churchism" and sacerdotalism, philosophies which were inimical to Congregationalism in general and Dr Jefferis in particular.

After her husband's death, Mrs Jefferis sold "Elbury House",[4] and lived permanently at "Yelki", which remained in the family for many years.