When his brother, Charles, was deposed as ruling duke by a rebellion in 1830, William took over the government provisionally.

In 1831, a family law of the House of Welf made William the ruling duke permanently.

William left most government business to his ministers, spending most of his time at Oleśnica Castle in what is now southwestern Poland.

While William joined the Prussian-led North German Confederation in 1866, his relationship to Prussia was strained, since Prussia refused to recognize his paternal grandnephew Ernest Augustus, Crown Prince of Hanover, as his heir, because of the Duke of Cumberland's claim to the throne of Hanover.

His death caused a constitutional crisis for Brunswick that lasted until the accession of his paternal great grand-nephew Ernest Augustus, Duke of Brunswick (a male line descendant of William, the younger brother of Henry, his male line ancestor), in 1913.