They left just before noon ... for St. Paul, Minnesota, registered at the Grand Hotel [Page 443 The Life of Mark Twain - The Middle Years 1871-1891]

Sam wrote from St. Paul to Livy, who’d asked if Pond ever failed to mail his letters. Sam didn’t think so and told the story of Orion taking one of his letters to the post box and when he got there forgetting why he’d gone, returning with the letter still in his pocket. Sam also related walking nine blocks to see the “ghost,” a “mysterious something on a school-house window pane,” which various people saw as various objects or persons. If all the fools in the world should die, lordy God how lonely I should be. Sam told of meeting old printer pals: In Quincy I saw—well, first it was an old man with bushy gray whiskers down to his breast, & farmer-like clothes on. When I saw him last, 35 years ago, he was a dandy, with plug hat tipped far forward & resting almost on his very nose; dark red, greasy hair, long, & rolled under at the bottom, down on his neck; red goatee; a most mincing, self-conceited gait—the most astonishing gait that ever I saw—a gait possible nowhere on earth but in our South & in that old day; & when his hat was off, a red roll of hair, a recumbent curl, was exposed (between two exact partings) which extended from his forehead rearward over the curve of his skull, & you could look into it as you would into a tunnel. But now—well, see Holmes’s “the Last Leaf” for what he is not. And there also I saw Wales McCormick, the giant printer-cub of 35 years ago—he & I were apprentices & the above dude, Pet McMurry, was the journeyman [MTP].

"Any one ignorant of the humorist's identity would have taken him for one of the chief mourners at a well-regulated funeral, or a life-long victim of dyspepsia and melancholia, in the acutest forms. He began business at once. His voice was the same old, characteristic nasal drawl, in which the public refused to see anything eloquent, or even pleasing, when he essayed (unsuccessfully) to be a lecturer some ten years ago, but which is now accepted as almost as convulsive as the humorist's utterances themselves." Saint Paul Daily Dispatch 1885: 24 January, coutesy Touring with Cable and Huck

I have been unable to find a map of the route but according to Saint Paul Globe, January 24, 1885 page 7, the Milwaukee and St, Paul Railroad connected with La Crosse.  Fast Mail and La Crosse Express arrives in St. Paul at 3:25 p.m. (Except Sundays).  See Chicago, Milwaukee and St Paul Railroad.  The St. Paul and Chicago had completed a route along the west bank of the Mississippi River, from St. Paul to La Crescent.  There existed a railroad bridge between La Crosse and La Crescent.