To provide the empirical evidence on usefulness of Problem Based Learning in a more controlled situation in Pre-service Teacher Education the present quasi-experimental research has examined the effects of Problem Based Learning (Independent variable) on 21st Century Learning and Innovation Skills which are also called 4C’s including Creativity, Critical Thinking, Collaboration and Communication (Dependent Variables) of prospective teachers. The lessons in the treatment group called Problem Based Learning (PBL) group were implemented according to the 7-steps of Problem Based Learning while the Non PBL method was followed in the control group called Non-PBL group in this study. A sample of two groups of female prospective teachers studying the course of Educational Research enrolled in Department of Education, International Islamic University Islamabad was taken for the study. One group (N=30) had been randomly assigned as control group and the other group (N=30) was assigned to be the experimental group. The experiment was conducted during Spring 2016 semester (i.e. February to June 2016). The self reported pre and post test were same and had items of sub-variables of 4c including critical thinking, creativity, collaboration and communication. The prospective teachers in experimental group described their experiences of learning the course through PBL. The pre-test and post-test data were analyzed by using mean scores and t-test through SPSS. The qualitative part of questionnaire was analyzed by coding the responses. No significant difference in mean scores of PBL and Non-PBL Groups were found on Pre-test on sub-scales of creativity, critical thinking, collaboration and communication. So it was confirmed that both the vi groups were equal before treatment. From the results of posttest, it was concluded that Non-PBL Method was not relatively an effective method for developing creativity, critical thinking, collaboration and communication of prospective teachers. It was established that Problem Based Learning was an effective method for developing creativity, critical thinking, collaboration and communication of prospective teachers. It may be determined that PBL is an effective method as compared to Non-PBL in developing creativity, collaboration and communication of prospective teachers. It may be determined that PBL is not very effective method as compared to Non-PBL in developing critical thinking of prospective teachers as evident from the scores of post test. Thus the prospective teachers gained good experiences with Problem Based Learning. They were satisfied with Problem Based Learning regarding development of different skills during the course. The teacher facilitated them during the course as is the actual role of teacher during Problem Based Learning. Difficulty in exploring material independently, then bringing it in the group, searching relevant material and non cooperation of some members were faced by prospective teachers during Problem Based Learning. The progression through Problem Based Learning takes some time and afterwards the learners become comfortable with this method. In the light of the conclusions, Problem Based Learning was recommended for teaching in pre-service teacher education for the course of Educational Research.