The 41 mostly originated as horsecar lines, albeit radial rather than crosstown.
The West Roxbury Railroad opened a horsecar line from Roxbury Crossing to Hyde Square in 1857, and extended it to JP Carhouse (South at Jamaica) in 1858. It was immediately leased by the Metropolitan Railroad, and used its Tremont Street line to reach downtown. A short extension to John Eliot Square also opened in 1858. There, it linked up with a loop on Roxbury and Dudley Streets, built by the Metropolitan in 1856, allowing West Roxbury cars to also use the Washington Street line. A parallel route between Jackson Square and John Eliot Square via Centre opened as a branch as far as Cedar in 1879, and was extended to Jackson Square in 1891. It was abandoned in 1925, though reused for bus service beginning in 1938 when what is now route 14 was added. Just about all those segments were electrified in 1891. The 41 was converted from streetcar to bus in 1949; it was rerouted over the Centre branch and cut back to Monument.
A horsecar branch on Dudley and Eustis from Washington to about Rockford opened in 1865, and was extended to Uphams Corner in 1865. (The short segment on Dudley between Washington and Eustis was filled in by the 1870s). That line was electrified in 1892. Routes 15 (Kane Square-Dudley) and 45 (Grove Hall-Dudley via Blue Hill Ave) were converted to trackless in 1948 and bus in 1962. The portion of Columbia Road between Uphams Corner and Edward Everett Square was opened as a horsecar line in 1860, closed in the 1880s, and reopened as a streetcar line around 1900. It was mostly used by what are now routes 16 and 17, which were converted to trackless in 1949 and bus in 1962.
The introduction of a Northampton - Savin Hill bus route in 1930 added service on Columbia as far east as Dorchester Avenue for the first time. Except for a brief period in 1962-63, that route used that segment until 1979. The remaining segment on Columbia between Dorchester Avenue and the station was briefly served by the 8 in 1962-63, again by the 8D variant in 1974, again by route 8 in 1977-78, and finally by route 8 beginning in 1984. Neither of those segments ever had streetcar lines.
Not until March 2002 was route 41 extended to JFK/UMass. That was the first time that Dudley-JFK/UMass service ran via Uphams Corner, though route 8 had connected the two by a different routing since 1973.