• A diagnosis of MF or post-ET or post-PV MF according to the 2016 World Health Organization (WHO) classification of MPN, confirmed by the most recent local pathology report

• Measurable splenomegaly during the screening period as demonstrated by spleen volume of greater than or equal to (\>=) 450 cubic square centimeter (cm\^3) by MRI or CT scan (results from MRI or CT imaging performed within 28 days prior to C1D1 are acceptable)

• DIPSS risk category of intermediate-1 with symptoms, or intermediate-2, or high-risk

• ECOG Performance Status less than or equal to (\<=) 2

• Platelet count of greater than or equal to (\>=) 50 x 10\^9/L without platelet transfusion within 7 days prior to the first dose of selinexor

• Absolute neutrophil count (ANC) \>=1.0 × 10\^9/L without need for growth factors within 7 days prior to the first dose of selinexor

• Adequate liver function as defined by the following: aspartate transaminase (AST) and alanine transaminase (ALT) \<= 2.5 × upper limit normal (ULN) and serum total bilirubin \<= 3×ULN

• Calculated creatinine clearance (CrCl) greater than (\>) 15 milliliter per minute (mL/min) based on the Cockcroft and Gault formula

• Active symptoms of MF as determined by presence of at least 2 symptoms with an average score \>= 5 or total score of \>= 12 at screening (at least 5 of 7 consecutive days immediately preceding C1D1) using the MFSAF V4.0

• Must provide bone marrow biopsy samples (samples obtained up to 3 months prior to C1D1 are permitted) at screening and during the study

• Currently not eligible for stem cell transplantation

• Must be willing to complete the MFSAF V4.0 daily during the study for evaluating the symptom response (i.e., TSS50)