Jefferis was a member of various Republican State and county committees. He was assistant county attorney for Douglas County, Nebraska, from 1896 to 1898. He ran in 1908 for the Sixty-first United States Congress and lost. He then became chairman of the Republican State convention in 1910. He succeeded in being elected to the Sixty-sixth and Sixty-seventh Congresses serving from March 4, 1919, to March 3, 1923. He ran unsuccessfully for the United States Senate in 1922 against Robert Beecher Howell.
Jefferis resumed the practice of law in Omaha. He was elected a delegate at large to the 1924 Republican National Convention. He was also the manager of the Coolidge-Dawes automobile caravan from Plymouth, Vermont, to Bellingham, Washington. He resumed his practice of law in Omaha, trying once more unsuccessfully candidate for United States Senator in 1940. He failed to get the nomination. He died at Omaha, Nebraska, on September 14, 1942, and is buried in Forest Lawn Cemetery, Omaha.