He succeeded his brother Johann Wilhelm, Elector Palatine on his death in 1716. He moved the Palatinate's capital from Heidelberg to the new city of Mannheim in 1720. Upon his death in 1742, the Palatinate-Neuburg line became extinct, and the Palatinate (including Neuburg, Jülich and Berg) was inherited by the Palatinate-Sulzbach line of the Wittelsbach family.
While in Mannheim, Karl III Philip, and later his nephew, put together what was commonly regarded as the finest orchestra in all of Europe. Under the leadership of musicians such as Johann Stamitz and Carlo Grua, the orchestra of the Kapelle was lauded by such musicians such as Leopold and Wolfgang Amadeus Mozart.
Karl Philipp married three times:
| Johann Wilhelm, Elector Palatine | Father: Philipp Wilhelm, Elector Palatine | Paternal Grandfather: Wolfgang Wilhelm, Count Palatine of Neuburg | Paternal Great-grandfather: Philipp Ludwig of Pfalz-Neuburg |
| Paternal Great-grandmother: Anna of Jülich-Cleves-Berg | |||
| Paternal Grandmother: Magdalene of Bavaria | Paternal Great-grandfather: William V, Duke of Bavaria | ||
| Paternal Great-grandmother: Renata of Lorraine | |||
| Mother: Elisabeth Amalie of Hesse-Darmstadt | Maternal Grandfather: George II, Landgrave of Hesse-Darmstadt | Maternal Great-grandfather: Louis V, Landgrave of Hesse-Darmstadt | |
| Maternal Great-grandmother: Magdalena of Brandenburg | |||
| Maternal Grandmother: Sophia Eleonore of Saxony | Maternal Great-grandfather: John George I, Elector of Saxony | ||
| Maternal Great-grandmother: Magdalene Sibylle of Prussia |