His mother engaged as tutor for Karl the Swiss scholar Frédéric Soret who became a close acquaintance to Johann Wolfgang von Goethe.

On 8 July 1853 his father died, and Karl Alexander became Grand Duke; however, he postponed his constitutional accession until Goethe's birthday, on 28 August 1853.

The Danish author and poet Hans Christian Andersen was reportedly infatuated with Karl Alexander, writing "I quite love the young duke, he is the first of all princes that I really find attractive".

In 1860, he founded the Grand-Ducal Saxon Art School in Weimar (with Arnold Böcklin, Franz von Lenbach, and the plastic artist Reinhold Begas).

At Kneuterdijk Palace in The Hague, on 8 October 1842, Karl Alexander married his first cousin, Princess Sophie of the Netherlands, daughter of William II and Grand Duchess Anna Pavlovna of Russia, sister of his mother.