Karl Weysser was born in Durlach as the tenth and last child of Mayor Friedrich Wilhelm Weysser and his wife Caroline. He grew up in the center of the small town, in a house on the market square across from the town church and the town hall.

From 1841 to 1848 he attended the high school in Durlach and then the Polytechnic School in Karlsruhe. In 1853 he moved to Berlin to the Friedrich Wilhelms University. In 1855 he returned to Karlsruhe, after completing his mathematical and technical studies, now also to study art at the newly founded Grand Ducal Baden Art Schoolto study. After the preparatory courses, Weysser specialized in architecture and landscape painting with Wilhelm Schirmer, later with Hans Gude.

Weysser completed his training in 1865, which included two longer stays in Munich in addition to other trips. Then he settled in Karlsruhe. From 1880 to 1884 he lived in Heidelberg, where he also wrote his first satirical work under the pseudonym KW Heissterpublished, which was followed by two more writings in later years. Although his writings are predominantly of a satirical nature, in the absence of any other written legacy they are important sources on the painter's personality.

In 1885 he married a much younger woman and moved to Baden-Baden , where he stayed until 1890. After two more changes of residence, he finally settled in Heidelberg in 1895, where he died in 1904.