During the 1880s and 1890s he continued to be one of the leading pamphleteers of the Young Czech party. He stopped practicing medicine and conducting scientific experiments in 1862 so that he could focus on a full-time political career. He became the Young Czech party's principal party speechmaker. Unlike his brother Julius, Eduard's temperament was characterized as very calm, warm and generous.
In the 1860s the Old Czech were the dominant party in Bohemian politics. They were criticized for abstaining from the election for the Bohemian Diet in protest against the centralist theories of the February Patent. Tensions rose when the Young Czechs supported the rebel cause during the Polish Revolution of 1863 and the Old Czechs condemned it. Julius and Eduard Grégr attacked the Old Czechs for sacrificing liberal nationalist goals in favor of the aims of the Bohemian feudal nobles during the accepted boycott of the Diet in Prague and the imperial Parliament in Vienna. Protests became widespread as the national discontent with the Old Czechs grew. This gave the Young Czechs a strong base of support to expand their political control.
After eight years (1871-79) of boycotting the Reichsrat in protest against the collapse of a negotiated agreement with Emperor Franz Joseph, the Young Czech chose to compromise. Their reentry into legislative politics marked the end of German Reichsrat majority. The Young Czechs held 85 to 87 of the 425 seats in the Reichsrat by 1900.
The supporters of the Young Czechs came from petty tradespeople, lawyers, progressive intellectuals, teachers and university students, some leaders in the Sokol gymnastic organization and middling farmers hurt by Hungarian and North American competition. Their followers believed in the liberal approach to the nationalist program prescribed by the Young Czechs rather than the more conservative approach of the Old Czechs.
In 1891, the end of the Old Czech predominance in Czech politics helped to disrupt the conservative “iron ring” parliamentary coalition with whose help Count Taaffe had governed since 1879, and marks the beginning of the modern era of Czech political parties.
From 1901 on, the party faced stern competition at the polls from newly founded parties that exploited weaknesses in the Young Czech social and economic programs and organizational structure. The Russian Revolution of 1905 stimulated strikes and other mass movements in the Czech Lands. In the parliamentary election of 1907 Young Czechs lost heavily to the Social Democrats and Agranians.
In February 1918, the party formally merged with a new coalition, the Czech State Right Democratic Party, which later, under the Republic, became the party of Czechoslovak National Democracy headed by Kramar.