Orion Clemens and his wife had settled there in June of 1855,  Sam, and younger brother Henry, helped Orion publish the Keokuk Journal out of a building at 202 Main Street.  Sam lived at First and Johnson Streets.  By late 18i55 Sam was across the river in Warsaw, Illinois working a for another newspaper. By the fall of 1856, Sam had left for Cincinnati.  Orion departed Keokuk for Nevada  but eventually returned to stay in 1872.

In 1882:

Keokuk was easily recognizable. I lived there in 1857—an extraordinary year there in real-estate matters. The 'boom' was something wonderful. Everybody bought, everybody sold—except widows and preachers; they always hold on; and when the tide ebbs, they get left. Anything in the semblance of a town lot, no matter how situated, was salable, and at a figure which would still have been high if the ground had been sodded with greenbacks.

The town has a population of fifteen thousand now, and is progressing with a healthy growth. It was night, and we could not see details, for which we were sorry, for Keokuk has the reputation of being a beautiful city. It was a pleasant one to live in long ago, and doubtless has advanced, not retrograded, in that respect.

A mighty work which was in progress there in my day is finished now. This is the canal over the Rapids. It is eight miles long, three hundred feet wide, and is in no place less than six feet deep. Its masonry is of the majestic kind which the War Department usually deals in, and will endure like a Roman aqueduct. The work cost four or five millions.

Interview 34 January 1885 Fort Madison (Iowa) Democrat; rpt Iowa Journal of History and Politics 27 (October 1929): 27-32  Included in "Mark Twain: The Complete Interviews" (#34)